HCV genotype 1 infection that cannot be subtypes should be treated as genotype 1a infection.

Approximately 10%-15% of HCV genotype 1-infected patients without prior exposure to NS5A inhibitors will have detectable HCV NS5A RAVs at the population level prior to treatment. While the clinical impact of NS5A RAVs remains to be fully elucidated, in patients with genotype 1a infection the presence of baseline NS5A RAVs that cause a large reduction in the activity of NS5A inhibitors (>5 fold) adversely impact response to NS5A-containing regimens

Given that baseline NS5A RAVs are one of the strongest pre-treatment predictors of treatment outcome with certain regimens in patients with genotype 1a infection, testing for these RAVs prior to deciding on a therapeutic course is recommended in select situations. (Zeuzem, 2015c)

The presence of certain baseline NS5A RAVs appears to be the single best predictor of relapse with the 12-week elbasvir/grazoprevir regimen

Extension of therapy to 16 weeks or 18 weeks with the addition of weight-based ribavirin increased response rates to 100% regardless of presence of baseline NS5A RAVs, suggesting this approach can overcome the negative impact of NS5A RAVs seen in the 12-week arms

Based on the known inferior response in patients with specific NS5A RAVs, NS5A resistance testing is recommended in genotype 1a patients who are being considered for therapy with elbasvir/grazoprevir. If these RAVs are present, treatment extension to 16 weeks with the addition of weight-based ribavirin (1000 mg [<75 kg] to 1200 mg [≥75 kg]) is recommended to decrease the risk of relapse.

Lack of RAV testing results or lack of access to RAV testing should not be used as a means to limit access to HCV therapy.

Some medicines cannot be taken with Zepatier – including prescription and over-the-counter medicines, vitamins, and herbal supplements

This regimen was given for 12 weeks or 24 weeks, with or without ribavirin

This regimen was well tolerated in all groups, with no serious adverse events reported in the 12-week regimen with or without ribavirn.

In the population with cirrhosis, patients treated for 24 weeks had higher SVR rates than those treated for 12 weeks, supporting the recommendation that HCV treatment-experienced patients with cirrhosis receive 24 weeks of treatment without ribavirin.

ledipasvir/sofosbuvir plus ribavirin for 12 week was similar to ledipasvir/sofosbuvir for 24 weeks

Baseline NS5A RAVs adversely impact responses to ledipasvir/sofosbuvir therapy; though the magnitude of this impact varies based on a number of factors including virus (genotype subtype, specific RAV), regimen (companion drugs, use of ribavirin), and patient factors (treatment experience, presence of cirrhosis).

The impact is likely to be larger in a genotype 1a only population. Given the vulnerable nature of this population, baseline NS5A resistance testing should be considered in genotype 1a treatment-experienced patients with cirrhosis prior to use of ledipasvir/sofosbuvir. If ledipasvir associated RAVs are detected consideration should be given to adding weight-based ribavirin to the regimen and extending therapy to 24 weeks

The single treatment-experienced patient who did not have a response to this regimen was a genotype 1b black patient with cirrhosis and IL28 TT genotype who had a persistently detectable HCV viral load during previous PEG-IFN/ribavirin therapy.

This regimen was well tolerated and there was no significant difference in the rate of adverse events in the sofosbuvir/velpatasvir group (78%) when compared to the placebo group (77%).

In antiretroviral-naive patients with a CD4 count greater than 500 cells/mm3, antiretroviral therapy could be deferred until after treatment of HCV.

For those patients whose CD4 counts are less than 200 cells/mm3 it may be advisable to first initiate antiretroviral therapy and defer HCV therapy until the patient is stable on antiretroviral therapy.

Epclusa (can be used with most regimen):

Okay with Triumeq

Okay with TAF OR TDF (Genvoya) if CrCl > 60. Velpatasvir increases the level of TAF or TDF e

Harvoni (can be used with most regimen)

Okay with TAF or TDF (Genvoya) if the baseline creatinine clearance is greater than 60 ml/min. Ledipasvir increases level of TAF or TDF

The HIV entry criteria required a CD4 count greater than 350 cells/mm3 if the patient was not taking antiretroviral therapy or at least 100 cells/mm3if on antiretroviral therapy and an HIV RNA less than 50 copies/ml

12 wk is needed. 8 wk was not enough

C212:

C-Edge confection (1,4,6)

elbasvir-grazoprevir once daily for 12 weeks

86% had genotype 1a or 1b infection and 35 (16%) had compensated cirrhosis